bimosiamose   Click here for help

GtoPdb Ligand ID: 9049

Synonyms: compound 15e [PMID: 9544210] [4] | TBC 1269 | TBC-1269 | TBC1269
Immunopharmacology Ligand
Compound class: Synthetic organic
Comment: Bimosiamose is a synthetic pan-selectin antagonist [4] being investigated as a novel anti-inflammatory agent, primarily for controlling allergic respiratory diseases [7,9], but it has also been reported to provide benefit in ischemia/reperfusion injury [1-2,5-6,8]. The primary role of selectin inhibitors appears to be disruption of early events in the migration process (possibly mediated through E-selectin [3]), thereby inhibiting their eventual extravasation from blood to the inflammed tissue.
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Ligand Activity Visualisation Charts

These are box plot that provide a unique visualisation, summarising all the activity data for a ligand taken from ChEMBL and GtoPdb across multiple targets and species. Click on a plot to see the median, interquartile range, low and high data points. A value of zero indicates that no data are available. A separate chart is created for each target, and where possible the algorithm tries to merge ChEMBL and GtoPdb targets by matching them on name and UniProt accession, for each available species. However, please note that inconsistency in naming of targets may lead to data for the same target being reported across multiple charts.

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View interactive charts of activity data across species
2D Structure
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2D Structure

An image of the ligand's 2D structure. For small molecules with SMILES these are drawn using the NCI/CADD Chemical Identifier Resolver. Click on the image to access the chemical structure search tool with the ligand pre-loaded in the structure editor. For other types of ligands, e.g. longer nucleotides and peptides, a manually drawn representation of the molecule may be provided.

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Physico-chemical Properties
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Physico-chemical Properties

Calculated molecular properties are available for small molecules and natural products (not peptides). Properties were generated using the CDK toolkit. All properties were selected to enable the prediction of the Lipinski Rule-of-Five profile or ‘druglikeness’ for each ligand. For more info on each category see the help pages.

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Hydrogen bond acceptors 14
Hydrogen bond donors 10
Rotatable bonds 19
Topological polar surface area 273.36
Molecular weight 862.34
XLogP 5.95
No. Lipinski's rules broken 4
SMILES / InChI / InChIKey
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SMILES / InChI / InChIKey

SMILES (Simplified Molecular Input Line Entry Specification) A specification for unambiguously describing the structure of chemical molecules using short ASCII strings. Canonical SMILES specify a unique representation of the 2D structure without chiral or isotopic specifications. Isomeric SMILES include chiral specification and isotopes.

Standard InChI (IUPAC International Chemical Identifier) and InChIKey InChI is a non-proprietary, standard, textual identifier for chemical substances designed to facilitate linking of information and database searching. An InChIKey is a simplified version of a full InChI, designed for easier web searching.

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Canonical SMILES OCC1OC(Oc2ccc(cc2c2cccc(c2)CC(=O)O)CCCCCCc2ccc(c(c2)c2cccc(c2)CC(=O)O)OC2OC(CO)C(C(C2O)O)O)C(C(C1O)O)O
Isomeric SMILES OC[C@H]1O[C@H](Oc2ccc(cc2c2cccc(c2)CC(=O)O)CCCCCCc2ccc(c(c2)c2cccc(c2)CC(=O)O)O[C@H]2O[C@H](CO)[C@H]([C@@H]([C@@H]2O)O)O)[C@H]([C@H]([C@@H]1O)O)O
InChI InChI=1S/C46H54O16/c47-23-35-39(53)41(55)43(57)45(61-35)59-33-15-13-25(19-31(33)29-11-5-9-27(17-29)21-37(49)50)7-3-1-2-4-8-26-14-16-34(60-46-44(58)42(56)40(54)36(24-48)62-46)32(20-26)30-12-6-10-28(18-30)22-38(51)52/h5-6,9-20,35-36,39-48,53-58H,1-4,7-8,21-24H2,(H,49,50)(H,51,52)/t35-,36-,39-,40-,41+,42+,43+,44+,45+,46+/m1/s1
InChI Key RYWCQJDEHXJHRI-XJMXIVSISA-N
References
1. Anaya-Prado R, Pérez-Gomez N, Toledo-Pereyra LH, Walsh J, Jordan J, Ward PA. (2008)
Small molecule selectin inhibitor in global cerebral ischemia and controlled hemorrhagic shock.
J Trauma, 65 (3): 678-84. [PMID:18784584]
2. Calvey CR, Toledo-Pereyra LH. (2007)
Selectin inhibitors and their proposed role in ischemia and reperfusion.
J Invest Surg, 20 (2): 71-85. [PMID:17454392]
3. Hicks AE, Abbitt KB, Dodd P, Ridger VC, Hellewell PG, Norman KE. (2005)
The anti-inflammatory effects of a selectin ligand mimetic, TBC-1269, are not a result of competitive inhibition of leukocyte rolling in vivo.
J Leukoc Biol, 77 (1): 59-66. [PMID:15466915]
4. Kogan TP, Dupré B, Bui H, McAbee KL, Kassir JM, Scott IL, Hu X, Vanderslice P, Beck PJ, Dixon RA. (1998)
Novel synthetic inhibitors of selectin-mediated cell adhesion: synthesis of 1,6-bis[3-(3-carboxymethylphenyl)-4-(2-alpha-D- mannopyranosyloxy)phenyl]hexane (TBC1269).
J Med Chem, 41 (7): 1099-111. [PMID:9544210]
5. Nemoto T, Burne MJ, Daniels F, O'Donnell MP, Crosson J, Berens K, Issekutz A, Kasiske BL, Keane WF, Rabb H. (2001)
Small molecule selectin ligand inhibition improves outcome in ischemic acute renal failure.
Kidney Int, 60 (6): 2205-14. [PMID:11737594]
6. Onai Y, Suzuki J, Nishiwaki Y, Gotoh R, Berens K, Dixon R, Yoshida M, Ito H, Isobe M. (2003)
Blockade of cell adhesion by a small molecule selectin antagonist attenuates myocardial ischemia/reperfusion injury.
Eur J Pharmacol, 481 (2-3): 217-25. [PMID:14642789]
7. Romano SJ, Slee DH. (2001)
Targeting selectins for the treatment of respiratory diseases.
Curr Opin Investig Drugs, 2 (7): 907-13. [PMID:11757789]
8. Toledo-Pereyra LH, Lopez-Neblina F, Reuben JS, Toledo AH, Ward PA. (2004)
Selectin inhibition modulates Akt/MAPK signaling and chemokine expression after liver ischemia-reperfusion.
J Invest Surg, 17 (6): 303-13. [PMID:15764497]
9. Vanderslice P, Biediger RJ, Woodside DG, Berens KL, Holland GW, Dixon RA. (2004)
Development of cell adhesion molecule antagonists as therapeutics for asthma and COPD.
Pulm Pharmacol Ther, 17 (1): 1-10. [PMID:14643165]
10. Watz H, Bock D, Meyer M, Schierhorn K, Vollhardt K, Woischwill C, Pedersen F, Kirsten A, Beeh KM, Meyer-Sabellek W et al.. (2013)
Inhaled pan-selectin antagonist Bimosiamose attenuates airway inflammation in COPD.
Pulm Pharmacol Ther, 26 (2): 265-70. [PMID:23257347]